We are studying the biochemical mechanism of membrane attack by complement proteins C5, C6, C7, C8 and C9. Membranes are attacked in two ways by these proteins, namely, by trans-membrane channel formation and by removal of phospholipid from the membrane. Our program is aimed at studying the mechanism of formation of channels, the factors which affect the efficiency of this process, the size and structure of the channels, their fluctuations and their overall life-span. In addition, we plan to investigate further the damage that is caused by phospholipid removal from cell membranes. The emphasis of our work is currently undergoing a progressive shift from model studies with erythrocytes and artificial membranes to investigations with mammalian nucleated cells. One of our major objectives is to learn why different target cells vary in their susceptibility to channel formation and, especially, why some nucleated cells, including certain tumor cells, are highly resistant to complement. We expect that this investigation will contribute significantly to our understanding of the function of complement in immune defense, and of its capacity to cause tissue damage in allergic and autoimmune diseases.